tbuckley/cabot-search huggingface dataset:
A phase II study of talimogene laherparepvec (T-VEC) and pembrolizumab in patients with advanced sarcoma: Results of expansion cohorts.
Authors: Ciara Marie Kelly, Viswatej Avutu, Ping Chi, Mark Andrew Dickson, Mrinal M. Gounder, Mary Louise Keohan, Sujana Movva, Evan Rosenbaum, Emma Cordover, Charlotte Eielson Ariyan, Edmund Bartlett, Aimee Marie Crago, Samuel Singer, Cristina R. Antonescu, Sinchun Hwang, Joseph Patrick Erinjeri, Kenneth Seier, Li-Xuan Qin, William D. Tap, Sandra P. D'Angelo
Journal: Journal of Clinical Oncology (2023)

11570 Background: The open-label, single-center phase II study of T-VEC and pembrolizumab in patients with advanced sarcoma met its primary endpoint and demonstrated a best objective response rate of 30% at 24 weeks per RECIST v1.1 (Kelly CM, et al, Jama Oncology, 2020). Responses were seen in undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma, (MFS), epithelioid sarcoma (ES), cutaneous angiosarcoma (AS), and undifferentiated sarcoma not otherwise specified. Here, we report the efficacy observed in three histology specific expansion cohorts: 1) UPS/MFS, 2) cutaneous AS and 3) ES. Methods: Patients refractory to ≥ 1 prior line of systemic therapy or declined standard of care systemic therapy received pembrolizumab intravenously and intratumoral T-VEC injections on day 1 of a 21-day cycle. The primary endpoint was best objective response (ORR, complete and partial responses per RECIST v 1.1) by 24 weeks estimated for each subtype-specific cohort. Secondary objectives included: adverse events (AEs, TRAEs), median PFS and correlatives. Results: Twenty-one patients enrolled in the expansion cohorts: median age 72 years (range: 39-85), male 57%, ≤ 1 prior line of therapy (43%). Treatment was well tolerated in twenty patients; one patient discontinued study therapy due to grade 3 immune mediated hepatitis. Nineteen patients were evaluable for efficacy (one patient withdrew from the study and another discontinued treatment before week 24). Subtype specific best ORR by 24 weeks per RECIST v 1.1: UPS/MFS – 11% (n = 1/9)[95% CI: 0.0-0.48]; AS – 43% (n = 3/7)[95% CI: 0.1-0.82]; ES – 0% (n = 0/3). The best ORR overall for the AS cohort was 71% (n = 5/7)[95% CI: 0.03-0.95]. Median PFS (weeks) was 14.9 [CI:7-111] for UPS/MFS and 54 [95% CI: 3- not reached] for AS (Table). Conclusions: TVEC and pembrolizumab demonstrated acceptable safety and promising anti-tumor activity in cutaneous AS [head &amp; neck (n = 4) and Stewart-Treves syndrome involving the upper extremity (n = 1)]. Five AS patients experienced a partial response with durable disease control, remaining on study for 1-2 years or more. Two delayed responses were observed in the AS cohort after the pre-specified 24-week criteria. One AS responder progressed on immune checkpoint inhibition prior to study entry. Correlative analyses are ongoing. Clinical trial information: NCT03069378 . [Table: see text]
Cancer survivorship: Patient experiences on early phase trials during the COVID-19 pandemic—Qualitative study from an Australian Phase 1 unit.
Authors: Oksana Zdanska, Anthony M. Joshua, Jia (Jenny) Liu, Pavel Zdansky, Melinda Stanners, Cath Rogers
Journal: Journal of Clinical Oncology (2023)

e24202 Background: The COVID-19 pandemic significantly disrupted global access to cancer care. Patient access to early phase trials during COVID-19 was maintained at our major tertiary Phase 1 unit using split teams, remote monitoring, direct to patient drug delivery and telehealth 1 . While there is substantial research focused on trial access, patient experiences of early phase treatment during the pandemic have not been documented. This research aims to identify early phase trial patients’ needs and provide insight into patients’ journey while receiving novel therapy in the midst of the Australian lockdown. Methods: This qualitative study recruited early phase trial participants with advanced /metastatic cancer treated at St Vincent’s Hospital, Sydney between 2020-2022 whilst the government-mandated lockdown was effective. Participants were audio/video recorded during their interview using a semi-structured approach. Thematic analysis was used to analyse patient stories and identify unmet needs. Analyses were performed using NVivo. Results: Nine clinical trial participants (five females, four males; five new trial participants, four known exceptional responders) consented and completed the in-depth interview (1-2.5 hours). Participants reported that COVID-19 created additional burden at a time of vulnerability, including challenging travel logistics, such as frequent travel exemption requests or need to relocate to access treatment, worsening anxiety and financial toxicity. COVID-19 lockdown induced separation from family abroad, touch deprivation and reduced psychological support for those with advanced cancer needing support, but provided more flexible work arrangements, allowing patients to work from home whilst on treatment. Conclusions: This study revealed unique social, psychological, logistical and financial challenges for cancer patients accessing early phase trials during the COVID-19 pandemic. Development of meaningful patient centred resources and supportive care interventions is needed to assist trial participants. 1 N Aggarwal et al (2022), Impact of COVID-19 on early phase clinical trials recruitment and treatment in a major metropolitan Phase 1 Unit, Poster Abstracts. Asia-Pac J Clin Oncol, 18: 33-51. https://doi.org/10.1111/ajco.13856.
Delayed immune toxicities in patients with breast cancer receiving immune checkpoint inhibitors.
Authors: Saya Jacob, Zoe Quandt, Michelle E. Melisko, Melanie Majure, Amy Jo Chien, Anne Hudson Blaes, Diane Heditsian, Laura Esserman, Hope S. Rugo
Journal: Journal of Clinical Oncology (2023)

e24091 Background: Immune checkpoint inhibitors (ICI) have improved outcomes in patients with breast cancer, however management of immune-related adverse events (irAE) remains a challenge. Delayed irAE after cessation of ICI have been observed. We sought to characterize delayed irAE occurring at our center. Methods: We identified patients with breast cancer who received ICI at UCSF using ICD codes specific to ICI administration between 2012-2018. After IRB approval, charts were reviewed for delayed irAE. Delayed irAE were defined as occurring &gt;60 days after the last ICI dose; events were counted as irAE if provider notes indicated that the toxicity was/possibly was related to ICI. Data were securely stored using RedCap. Results: We reviewed 100 consecutive patients who underwent ICI (56 metastatic, 44 localized) of which 11 (2 (4%) with metastatic disease, 9 (20.5%) with localized disease) developed delayed irAE. Median age was 42. 3 patients had HR+ disease, 8 patients had triple negative disease. 10 patients received ICI on a clinical trial, including 9 on the neoadjuvant ISPY2 trial. 10 patients received pembrolizumab; 1 received durvalumab. Median number of ICI doses was 4, median follow-up time after last ICI infusion was 46 months. 14 incidences of delayed irAEs were identified (Table). 9 patients experienced both delayed and early irAE. 7 patients experienced 2 irAEs: 1) three dermatitis &amp; delayed hypophysitis/adrenal insufficiency (AI) 2) one AI &amp; delayed thyroiditis 3) one dermatitis and delayed colitis 4) one elevated transaminases &amp; delayed colitis 5) one delayed elevated transaminases and delayed thyroiditis. One patient had 3 irAEs (thyroiditis, delayed AI &amp; delayed arthralgia) and one patient had 4 irAE (colitis, dermatitis, delayed elevated transaminases &amp; delayed neutropenia). Of the 9 patients with &gt; 1 irAE, 3 experienced &gt; 1 delayed irAE (thyroiditis + elevated transaminases; arthralgia + AI; elevated transaminases + neutropenia). All irAE either self-resolved, resolved with systemic steroids or indefinite hormone replacement. 6 irAEs required systemic steroids, not including hydrocortisone replacement for AI. Conclusions: Delayed irAE may occur months after ICI cessation and require awareness for identification. Patients who experience irAE may be more likely to develop additional irAE at either a delayed or earlier time point. Most patients with delayed irAE experienced an irAE at an early time point. Future directions include identifying risk factors for early and delayed irAEs to inform treatment decisions. [Table: see text]
Comparison among three predictive models for cancer-associated thromboembolism in a Hispanic population.
Authors: Allan Ramos-Esquivel, Gabriel Hernández-Romero, Ana Marenco-Flores, Carlos Umaña, Ana Céspedes-Calvo, Raquel Mora-Hidalgo
Journal: Journal of Clinical Oncology (2023)

e24074 Background: Several predictive scores have been developed to assess the risk of venous thromboembolism (VTE) among cancer patients. Although their use is currently recommended by several guidelines, it is unknown if these scores can accurately predict the risk of VTE in Hispanic patients that are at different risk for thrombosis. Methods: We retrospectively evaluated all outpatients with newly diagnosed solid tumors receiving systemic chemotherapy in Hospital San Juan Dios, San José, Costa Rica, from January to December 2021. For each patient, the Khorana, PROTECHT, and CONKO scores were calculated at the beginning of treatment. The sixth-month cumulative incidence of VTE was estimated using the Fine &amp; Gray competing risk model for the overall population and stratified according to each risk category. A Kaplan-Meier analysis was used to compare the cumulative VTE incidences between high- and low-risk categories of the three predictive scores. The Cox regression analysis was used to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI). The receiver operating characteristic (ROC) curve was used to assess the performance of each predictive tool through the analysis of the c-statistic, sensitivity, and specificity. Results: 708 patients were included in the analysis. After a median follow-up of 8.13 months, the cumulative VTE incidence at six months was 4.45% (95%CI: 3.25-6.91%). At the conventional positivity threshold of 3 points, these scores classified from 17.7 to 27.5% of all patients as high-risk for VTE. The 6-month incidence of VTE among high-risk patients ranged from 7.6% for the Khorana score to 9.3% for the CONKO score. Patients belonging to the high-risk category of the Khorana, PROTECHT, and CONKO scores had significantly higher risk of VTE in comparison to low-risk patients (Khorana score: HR: 2.66; 95%CI:1.20-5.89; p = 0.042; PROTECHT score: HR: 3.44; 95%CI:1.63-7.21; p = 0.001; CONKO score HR: 3.68; 95%CI:1.72-7.85; p = 0.001). Table 1 resumes the performance of the studied scores. Table 1. Performance of the Khorana, PROTECHT, and CONKO scores for the prediction of venous thromboembolism. Conclusions: The Khorana, PROTECHT, and CONKO scores accurately predict the risk of VTE in Hispanic patients with solid tumors with similar performance among them. However, their sensitivity and specificity remain poor for identifying all patients at risk for thromboembolic events.[Table: see text]
The financial toxicity of chemotherapy in Belize.
Authors: Wayne Wong, James Dickerson, John Lattin, Alec Ohanian, Marta Habet, Margaret Bernard, Franklin W. Huang, Ramoncito Argenes Yacab
Journal: Journal of Clinical Oncology (2023)

e24007 Background: In low- and middle-income countries (LMICs) such as Belize, large fractions of healthcare costs are borne directly by patients. In these settings of minimal insurance coverage and a fragmented healthcare system, evaluating the extent of financial toxicity is paramount to understanding direct barriers to care delivery. We surveyed Belizean cancer patients in 2022 who were receiving chemotherapy at the only public oncology clinic in the country, established at the Karl Heusner Memorial Hospital (KHMH) in 2018, to quantify financial toxicity. Methods: A convenience sample of patients at the KHMH oncology clinic were surveyed between February and March 2022. Patients who consented during their infusion appointment were given a tablet with a 21-question survey (English or Spanish). This survey was developed from the FACT-G and COST tools adapted specifically for LMIC settings. Answers were on a 5-point Likert scale. We provide descriptive statistics of the population and survey responses. Results: Median age of survey participants (n = 32) was 51 (IQR 43 – 62), 84% were female and 53% unemployed. 71% were uninsured. Those insured were covered by the Belizean government’s National Health Insurance which does not include oncologic care. Most patients (72%) had traveled from another district for treatment at the clinic in Belize City. Cancer types represented were breast (42%), gastrointestinal (27%), gynecologic (27%), and lymphoma (4%); 75% of patients had either stage 3 or 4 disease. 56% agreed with the statement “I am having financial problems with cancer treatment,” 31% disagreed, and 13% neither agreed nor disagreed. Patients were allowed to indicate multiple contributors to financial hardship during treatment, with costs of chemotherapy cited most often (50% of patients), followed by transportation costs (38%), hospital fees (22%), food (12%), and housing (9%). 25% of respondents agreed with the prompt “It is difficult to come to all of my appointments,” with transportation being the most cited reason (88%). Conclusions: In our survey, more than half of Belizean cancer patients on chemotherapy reported financial hardship with their treatment. Drivers of toxicity were the cost of chemotherapy and travel. Our sample, predominately female, unemployed, uninsured, and from less wealthy districts, had sociodemographic factors that suggest a high risk for financial toxicity during cancer treatment. Though limited by the small sample size, this study prompts further investigation and more precise quantification of financial toxicity in Belize. These preliminary data have begun conversations within the Ministry of Health for inclusion of chemotherapy under the covered medications list by public health institutions.
Nutrition and head-neck cancer: A prospective observational study in patients with head neck cancer receiving adjuvant/definitive radiotherapy/chemoradiotherapy.
Authors: Dr Chetan Dilip Deshmukh, Dr Mukesh Chaudhary, Padmaj Sudhakar Kulkarni, Sachin Sharadchandra Hingmire
Journal: Journal of Clinical Oncology (2023)

e18784 Background: Head-Neck cancers are at higher risk of malnutrition due to their disease or its treatment which can cause structural changes to the oral cavity and prevent effective nutrition. Malnutrition is assessed by anthropometric measurements. Skeletal muscle strength is also a marker of nutrition. The present study aimed to study the correlation between nutrition, muscle strength and acute toxicities in patients with head and neck squamous carcinoma receiving concurrent chemoradiotherapy or radiotherapy alone. Methods: A prospective observational study was conducted at Deenanath Mangeshkar Hospital, Pune, India in patients with nonmetastatic head neck squamous cancers planned for definitive or adjuvant chemo-radiotherapy. Nutritional status was assessed at baseline, end of treatment and after 3months of treatment by mid-arm circumference, weight, height and body mass index. Muscle strength was assessed by Jamar’s handgrip dynamometer. Results: A total of 103 patients (85 males and 18 females) participated in the study between February 2020 and February 2021. Four patients had to be withdrawn before initiating treatment, 99 patients completed the planned course of treatment. Mean age was 54.4 years. Postoperative chemoradiotherapy was give to 37 patients, 22 received definitive chemoradiotherapy, 33 received postoperative radiotherapy alone and 7 patients received definitive radiotherapy. A statistically significant reduction in all nutritional parameters during treatment and at 3 months after completion of treatment was seen. Mucositis and odynophagia were the commonest toxicities. Nasogastric or percutaneous gastrostomy tube was inserted in 25 patients. Seven patients required hospitalisation for toxicities. There were no treatment related deaths. Conclusions: Head and neck cancer patients undergoing concurrent chemoradiation or radiation are at significantly higher risk of malnutrition. Loss of muscle strength correlates with treatment related acute toxicity. [Table: see text]
How comparable are outcomes for approved PD-1/PD-L1 checkpoint inhibitors (CPI)? A model-informed drug development approach to answer the question.
Authors: Molly Zhao, Naveen Mangal, Han Witjes, Matthew L Zierhut, Ting Chen, Thao Dang, Sandhya Girish, Sreeneeranj Kasichayanula
Journal: Journal of Clinical Oncology (2023)

e21152 Background: Treatment strategies in metastatic non-small cell lung cancer (mNSCLC) have been implemented by anti-PD-(L)1 based therapies. This work aimed to develop a model-based meta-analysis (MBMA) to compare ORR, median PFS (mPFS), median OS (mOS), and treatment-related adverse events Grade 3-5 (TRAEs Gr3+) among anti-PD-(L)1 therapies in mNSCLC. Methods: A curated database of phase 1, 2, and 3 study results in mNSCLC patients treated with at least one FDA-approved PD-(L)1 CPI was used for these analyses. The ORR, mPFS, mOS, and TRAEs Gr3+ analysis datasets included results from 40, 39, 35 and 45 studies, and represented 13324, 13220, 13029, and 21077 patients, respectively. Treatments included: platinum doublet (Pt), pembrolizumab (+/- Pt), nivolumab (+/- Pt and +/- ipilimumab), atezolizumab (+/- Pt), and cemiplimab. Models were developed to quantify drivers of variability on outcomes across trials (i.e., treatment, covariates, random effects). The following covariates were evaluated: PD-L1 expression, line of therapy, ECOG PS, histology, geography/race, sex, age, and smoking status. Results: Treatment naïve patients showed better efficacy than treatment experienced patients, while higher PD-L1 expression was associated with improvement for CPI-containing therapies. Asian-majority trials and patients with PS 0 achieved higher mOS. After adjusting for covariates, similar efficacy was observed across PD-(L)1 within both mono- and combination therapy groups (Table 1). No clinically meaningful covariates were identified for TRAEs Gr3+. Rates were comparable between chemotherapy +/- PD-(L)1, but lower for PD-(L)1 monotherapy. Conclusions: MBMA enables an appropriate comparison of CPI-containing therapy using published study results. To our knowledge, this is the first such analysis in mNSCLC comparing efficacy and safety across PD-(L)1 based therapies. Results suggest PD-(L)1 CPI have similar treatment outcomes in mNSCLC, and PD-L1 expression may be more impactful on clinical benefit of monotherapy compared to CPI combination with chemotherapy. [Table: see text]
Effect and safety of combining bevacizumab and fractionated stereotactic radiotherapy for brain metastases in patients with non-small cell lung cancer: A phase II trial.
Authors: Rui Zhou, ShiYang Zheng, LanQing Huo, QiaoTing Luo, DaQuan Wang, JinYu Guo, BiaoShui Liu, Jun Zhang, Bin Wang, Bo Qiu, Hui Liu
Journal: Journal of Clinical Oncology (2023)

e21132 Background: W e aimed to assess the efficacy and safety of c ombining b evacizumab and fractionated stereotactic radiotherapy ( FSRT ) for brain metastases (BMs) in non-small cell lung cancer ( NSCLC ) patients with stable extracranial disease status in this study. Methods: NSCLC patients with BMs were recruited between J anuary 20 20 and J anuary 202 2 . P atients were assigned to receive FSRT of 40Gy in 10 fractions (BED 56eGy) or 30Gy in 5 fractions (BED 48eGy). Meanwhile, bevacizumab was administered before FSRT (d1) and after FSRT (d21) with a dosage of 7.5mg/Kg. The primary endpoint of the study is intra-cranial progression-free survival (IPFS) . The secondary endpoints contained overall survival (OS), progression-free survival (PFS) , quality of life (QOL) score and toxicities. All time-to-event endpoints (IPFS, OS and PFS) were measured from the end of radiotherapy. Results: From J anuary 2020 and J anuary 202 2, 108 patients were recruited with a median follow-up duration was 15.2 months . The 1-year IPFS and OS rate were 82.9% ( 95% confidence interval (CI), 79.6%-86.2% ) and 80.4% ( 95% CI, 76.8%-84.0% ), respectively . The median PFS was 15.0 months ( 95% CI, 9.50-20.50 months ). The median IPFS and OS had not been reached at the time of the last follow-up. The treatment-related toxicities were mild with low incidence. Reversible mild hypertension and cerebral radio-necrosis were observed in 2 and 1 patients, respectively. No signs of ex tra-lesional haemorrhage and progression of peri-lesional oedema was found during the assessment period of treatment response. More importantly, significant improvent of QOL was observed in symptomatic patients. Conclusions: The combination of FSRT with bevacizumab in patients with NSCLC was well tolerated and achieved promising intracranial disease control. Patients maintained satisfactory QOL after receiving the combined regimen with low incidence of cerebral radio-necrosis. Clinical trial information: NCT04345146 .
Assessment of HER2 status in extramammary Paget disease and its implication for disitamab vedotin, a novel humanized anti-HER2 antibody-drug conjugate (ADC) therapy.
Authors: Lu Si, Jia Jia, Lili Mao, Jing Lin, Pei Yuan, Wen Yu Li, Jie Dai, Zhong-Wu Li, Xue Bai, Caili Li, Lei Guo, Yu Chen, Jianming Ying, Jun Guo
Journal: Journal of Clinical Oncology (2023)

e21544 Background: Evaluation of HER2 status in extramammary Paget disease (EMPD) has been reported in a few studies with a small number of samples, and the HER2 overexpression rate ranges from 15% to 60%. The prognosis of advanced EMPD is poor and the treatment options is limited. Disitamab Vedotin (DV) is a novel humanized anti-HER2 antibody-drug conjugate (ADC), has been approved for metastatic urothelial carcinoma and gastric cancer in China. To determine the HER2 status and the efficacy of DV in advanced EMPD patients (pts) harboring HER2 expression, we conducted this multicenter retrospective study. Methods: Paraffin-embedded blocks, clinic-pathological data, and survival data of EMPD pts were retrospectively collected from 3 centers in China. HER2 IHC scoring and gene amplification evaluation were carried out according to the (ASCO/CAP) 2018 guidelines. The results of FISH and IHC were analyzed by two pathologists independently in a double-blinded manner. Data analysis was performed using SPSS v.26, Prism 8 and R version 3.6.5. Results: Finally, 129 cases with detailed data were enrolled between 2006 and 2022. Among them, HER2 IHC was performed in 102 cases, and FISH in 46 cases. HER2 expression was detected in 93.1% samples, with scores of 1+, 2+, and 3+ in 47.1% (48/102), 37.3% (38/102), and 8.7% (9/102) respectively. HER2 gene amplification was detected in eight cases (8/46, 17.4%), including all the cases with IHC 3+ (5/5, 100%), two with IHC 2+ (2/18, 11.1%), and one with IHC 1+ (1/22, 4.5%). For the subgroup of HER2 2+/3+, a higher frequency of lymph node metastasis (66.7% vs 33.3%, P = 0.034) and reduced survival time were detected than in HER2 1+/0. Two elderly male pts with advanced EMPD (one HER1+ /FISH-, one HER 2+/FISH-), who failed with chemo of paclitaxel, received 4 doses of DV infusion (2mg/kg every 2 weeks), and achieved partial responses both with tolerable toxicity. Conclusions: According to the study, the expression rate of HER-2 was very high in EMPD, indicating that it may be used as a routine treatment target. DV showed efficacy in these patients and need further validation.